OBJECTIVES: In 2012, the FDA issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias.  Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) commonly used to treat posttraumatic stress disorder (PTSD).  As minimal research has assessed drug-related QT prolongation in patients with severe mental illnesses, this study explores psychotropic drugs associated with QT prolongation among Veterans diagnosed with PTSD.  METHODS: Patients with PTSD in the Veterans Health Administration in 2006-2009 were reviewed, identifying 176 Veterans diagnosed with QT prolongation.  Cases were matched 1:4 on age, gender, visit date and setting, and physical comorbidity.  Classification trees assessed QT prolongation risk among prescribed medications for the combined sample (N=880).  Finally, five-year survival by prolonged QT status was analyzed.  RESULTS: Receipt of any drug with known risk of QT prolongation varied by group (23% QT vs. 15% control, p<0.01).  Psychotropic medications conferring significant risks included the antipsychotic ziprasidone (3% vs. 1%, p=0.02) and the anxiolytic buspirone (6% vs. 2%, p=0.01) but not the SSRIs citalopram and fluoxetine.  Classification trees found sotalol and the tricyclic antidepressant amitriptyline carried greater risk among cardiac patients, and methadone, especially if prescribed with quetiapine, among non-cardiac patients.  Per preliminary adjusted survival model, patients with QT prolongation were at increased risk for mortality (HR=1.60; 95% CI: 1.04-2.44). CONCLUSIONS: Decision models are particularly advantageous when exploring nonlinear relationships or non-additive interactions.  These findings may potentially impact clinical decision-making concerning treatment for PTSD.  For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered.  Medications for comorbid conditions should also be closely monitored for heightened risk of QT prolongation.  This study further highlights the importance of routine use of electrocardiograms for QT monitoring among patients with PTSD taking these agents.